Mortal Simone, Iseppon Federico, Perissinotto Andrea, D'Este Elisa, Cojoc Dan, Napolitano Luisa M R, Torre Vincent
Neurobiology Department, International School for Advanced Studies, Trieste, Italy.
Department of NanoBiophotonics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Front Cell Neurosci. 2017 Dec 18;11:402. doi: 10.3389/fncel.2017.00402. eCollection 2017.
During neurite development, Actin Waves (AWs) emerge at the neurite base and move up to its tip, causing a transient retraction of the Growth Cone (GC). Many studies have shown that AWs are linked to outbursts of neurite growth and, therefore, contribute to the fast elongation of the nascent axon. Using long term live cell-imaging, we show that AWs do not boost neurite outgrowth and that neurites without AWs can elongate for several hundred microns. Inhibition of Myosin II abolishes the transient GC retraction and strongly modifies the AWs morphology. Super-resolution nanoscopy shows that Myosin IIB shapes the growth cone-like AWs structure and is differently distributed in AWs and GCs. Interestingly, depletion of membrane cholesterol and inhibition of Rho GTPases decrease AWs frequency and velocity. Our results indicate that Myosin IIB, membrane tension, and small Rho GTPases are important players in the regulation of the AW dynamics. Finally, we suggest a role for AWs in maintaining the GCs active during environmental exploration.
在神经突发育过程中,肌动蛋白波(AWs)在神经突基部出现并向上移动至其顶端,导致生长锥(GC)短暂回缩。许多研究表明,肌动蛋白波与神经突生长的爆发有关,因此有助于新生轴突的快速伸长。通过长期活细胞成像,我们发现肌动蛋白波并不会促进神经突生长,并且没有肌动蛋白波的神经突也可以伸长数百微米。抑制肌球蛋白II可消除生长锥的短暂回缩,并强烈改变肌动蛋白波的形态。超分辨率纳米显微镜显示,肌球蛋白IIB塑造了生长锥样的肌动蛋白波结构,并且在肌动蛋白波和生长锥中的分布不同。有趣的是,膜胆固醇的消耗和Rho GTP酶的抑制会降低肌动蛋白波的频率和速度。我们的结果表明,肌球蛋白IIB、膜张力和小Rho GTP酶是调节肌动蛋白波动力学的重要因素。最后,我们提出肌动蛋白波在环境探索过程中维持生长锥活性方面发挥作用。